PXD021858

PXD021858 is an original dataset announced via ProteomeXchange.

Title	ApoC-III is a novel inducer of human valvular calcification
Description	Pharmacological interventions to treat valvular calcification are not currently part of clinical guidelines. Low-density lipoprotein lowering therapies to treat calcific aortic valve disease (CAVD) failed in clinical trials. However, apolipoproteins are known promotors of atherosclerosis and may play a role in CAVD pathogenesis beyond their lipid-binding capabilities. Lipoprotein particles carry oxidized lipids that promote valvular disease, but whether apolipoproteins themselves possess pathogenic properties in CAVD is less clear. We assessed 12 apolipoproteins in non-fibrotic/non-calcific (NF/NC), fibrotic (F) and calcific (C) aortic valve tissues by proteomics and immunohistochemistry and evaluated effects of enriched apolipoproteins on calcification. Eight apolipoproteins (apoA-I, apoA-II, apoA-IV, apoB, apoC-III, apoD, apoL-I and apoM) were enriched in the C vs. NF/NC tissues. Apo(a), apoB, apoC-III, apoE and apoJ colocalized with the disease-prone fibrosa and calcific regions on histological sections. Circulating apoC-III on lipoprotein(a) was identified as a potential biomarker of aortic stenosis incidence and progression, but whether apoC-III also contributes to CAVD is unknown. ApoC-III was increased in F and C tissues and observed within the calcification-prone fibrosa layer as well as around calcification and induced calcification in primary human valvular cell cultures via a mitochondrial dysfunction/inflammation-mediated calcification pathway. This study provides the first assessment of a broad array of apolipoproteins in CAVD tissues, demonstrates that specific apolipoproteins associate with valvular calcification, and implicates apoC-III as an active, modifiable driver of CAVD beyond its potential role as a biomarker.
HostingRepository	PRIDE
AnnounceDate	2020-12-14
AnnouncementXML	Submission_2020-12-14_00:07:23.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sasha Singh
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-06 01:20:22	ID requested
⏵ 1	2020-12-14 00:07:23	announced

Dataset with its publication pending

submitter keyword: calcific aortic valve disease

valvular interstitial cells

fibrosis

lipids

apoC-III

Elena Aikawa
contact affiliation	Center for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
contact email	eaikawa@bwh.harvard.edu
lab head
Sasha Singh
contact affiliation	Brigham and Women's Hospital, Harvard Medical School
contact email	sasingh@bwh.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021858
     1. Label: PRIDE project
     2. Name: ApoC-III is a novel inducer of human valvular calcification